scholarly journals Role of Inflammation in Coronary Epicardial and Microvascular Dysfunction

2021 ◽  
Vol 16 ◽  
Author(s):  
Shigeo Godo ◽  
Jun Takahashi ◽  
Satoshi Yasuda ◽  
Hiroaki Shimokawa
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Vascular Inflammation ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Low Grade ◽  
Coronary Vasomotion ◽  
Close Relationship ◽  
Underlying Mechanisms

There is accumulating evidence highlighting a close relationship between inflammation and coronary microvascular dysfunction (CMD) in various experimental and clinical settings, with major clinical implications. Chronic low-grade vascular inflammation plays important roles in the underlying mechanisms behind CMD, especially in patients with coronary artery disease, obesity, heart failure with preserved ejection fraction and chronic inflammatory rheumatoid diseases. The central mechanisms of coronary vasomotion abnormalities comprise enhanced coronary vasoconstrictor reactivity, reduced endothelium-dependent and -independent coronary vasodilator capacity and increased coronary microvascular resistance, where inflammatory mediators and responses are substantially involved. How to modulate CMD to improve clinical outcomes of patients with the disorder and whether CMD management by targeting inflammatory responses can benefit patients remain challenging questions in need of further research. This review provides a concise overview of the current knowledge of the involvement of inflammation in the pathophysiology and molecular mechanisms of CMD from bench to bedside.

scholarly journals Coronary Microvascular Dysfunction: An Update

2020 ◽  
Vol 16 (1) ◽  
pp. 43-49
Author(s):  
Sm Mustafa Zaman ◽  
Harisul Hoque ◽  
Khurshed Ahmed ◽  
Md Mukhlesur Rahman ◽  
Msi Tipu Chowdhury ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Myocardial Perfusion ◽  
Current Knowledge ◽  
Systolic Dysfunction ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Resonance Spectroscopy ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Microvascular Angina

Structural and functional abnormalities of the microcirculation can impair myocardial perfusion which is called coronary microvascular dysfunction and the resulting ischemia is known as microvascular ischaemia. Most of the researches have focused on the epicardial coronary arteries while addressing angina pectoris. Although the importance of the coronary microcirculation in maintaining appropriate myocardial perfusion has been recognized for several decades, the substantial morbidity of coronary microvascular dysfunction (CMD) has not been appreciated until recently. It is not possible to diagnose of microvascular angina clinically with the current knowledge. Resting or exercise electrocardiogram is nondiagnostic. Imaging with speckle tracking in echocardiography may reveal focal diastolic and/or systolic dysfunction. Other noninvasive investigations includes, Contrast stress echocardiography, 99Tc-sestamibi imaging, cardiovascular magnetic resonance (CMR),Nuclear magnetic resonance spectroscopy may show some degree of abnormality. Invasive methods like intracoronary adenosine and acetylecholine test may guide us to diagnose CMD. No guideline directed medical therapy is still available for the CMD. Risk factors modification like smoking cessation and weight-loss may improve endothelial dysfunction and CMD. Beta blockers, calcium channel blockers, Angiotensin converting enzyme inhibitors and statin are now used in different clinical condition related to microvascular angina. After these medical treatment patient with microvascular angina have higher risk of MACE compared with people without angina. So, physicians must be aware of this potentially fatal but under recognized clinical entity. University Heart Journal Vol. 16, No. 1, Jan 2020; 43-49

Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions

2007 ◽  
Vol 112 (7) ◽  
pp. 375-384 ◽  
Author(s):  
Carmine Savoia ◽  
Ernesto L. Schiffrin
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Vascular Inflammation ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Low Grade ◽  
Cardiovascular Morbidity And Mortality

More than 80% of patients with type 2 diabetes mellitus develop hypertension, and approx. 20% of patients with hypertension develop diabetes. This combination of cardiovascular risk factors will account for a large proportion of cardiovascular morbidity and mortality. Lowering elevated blood pressure in diabetic hypertensive individuals decreases cardiovascular events. In patients with hypertension and diabetes, the pathophysiology of cardiovascular disease is multifactorial, but recent evidence points toward the presence of an important component dependent on a low-grade inflammatory process. Angiotensin II may be to a large degree responsible for triggering vascular inflammation by inducing oxidative stress, resulting in up-regulation of pro-inflammatory transcription factors such as NF-κB (nuclear factor κB). These, in turn, regulate the generation of inflammatory mediators that lead to endothelial dysfunction and vascular injury. Inflammatory markers (e.g. C-reactive protein, chemokines and adhesion molecules) are increased in patients with hypertension and metabolic disorders, and predict the development of cardiovascular disease. Lifestyle modification and pharmacological approaches (such as drugs that target the renin–angiotensin system) may reduce blood pressure and inflammation in patients with hypertension and metabolic disorders, which will reduce cardiovascular risk, development of diabetes and cardiovascular morbidity and mortality.

scholarly journals Clinico-pathophysiological considerations in coronary microvascular disorders

Vessel Plus ◽  
2022 ◽  
Author(s):  
Sarena La ◽  
Rosanna Tavella ◽  
Sivabaskari Pasupathy ◽  
John F. Beltrame
Keyword(s):  
Coronary Arteries ◽  
Myocardial Ischaemia ◽  
Pain Perception ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Microvascular Angina ◽  
Common Clinical Presentation ◽  
Microvascular Spasm ◽  
Underlying Mechanisms ◽  
Microvascular Resistance

Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

scholarly journals Testosterone inhibits aneurysm formation and vascular inflammation in male mice

2019 ◽  
Vol 241 (3) ◽  
pp. 307-317 ◽  
Author(s):  
Bo-Kyung Son ◽  
Taro Kojima ◽  
Sumito Ogawa ◽  
Masahiro Akishita
Keyword(s):  
Inflammatory Responses ◽  
Vascular Inflammation ◽  
Serum Testosterone ◽  
Epidemiologic Studies ◽  
Male Mice ◽  
Aortic Pathology ◽  
Wild Type Male ◽  
Testosterone Administration ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies

Abdominal aortic aneurysm (AAA), one of the pathological phenotypes of vascular aging, is characterized by aortic dilation with impaired arterial wall integrity. Recent epidemiologic studies have shown that men with AAA have lower serum testosterone compared to men without. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of testosterone on AAA formation using a murine AAA model under the conditions of depletion and administration of testosterone. In wild-type male mice (C57BL/6J), AAA was induced by CaCl2 application and angiotensin II infusion at 5 weeks after castration. Exacerbated AAA formation was seen in castrated mice, compared with sham-operated mice. Histological analysis revealed marked infiltration of macrophages in the destroyed aorta and IL-6/pSTAT3 expression was significantly elevated, suggesting that AAA development by castration is attributable to pronounced inflammation. Conversely, both 4-week and 9-week administration of testosterone significantly prevented AAA formation, and improvement of histological findings was confirmed. Aortic F4/80, Il-1b and Il-6 expression were significantly inhibited both by testosterone administration. Indeed, mice with implanted flutamide exhibited exacerbated AAA formation and aortic F4/80, Il-1b and Il-6 expression were significantly increased. Taken together, these results demonstrate that testosterone depletion and AR blockade precede AAA formation, and conversely, testosterone administration could suppress AAA formation by regulating macrophage-mediated inflammatory responses. This anti-inflammatory action of testosterone/AR on AAA formation might provide a mechanistic insight into the vascular protective actions of testosterone and suggest that its proper administration or selective AR modulators might be novel therapeutic strategies for this aortic pathology.

scholarly journals Effects and Mechanisms of Tea Regulating Blood Pressure: Evidences and Promises

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1115 ◽  
Author(s):  
Daxiang Li ◽  
Ruru Wang ◽  
Jinbao Huang ◽  
Qingshuang Cai ◽  
Chung S. Yang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Animal Studies ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Vascular Inflammation ◽  
Optimal Dose ◽  
Smooth Muscle Contraction ◽  
Beneficial Effects ◽  
Underlying Mechanisms

Cardiovascular diseases have overtaken cancers as the number one cause of death. Hypertension is the most dangerous factor linked to deaths caused by cardiovascular diseases. Many researchers have reported that tea has anti-hypertensive effects in animals and humans. The aim of this review is to update the information on the anti-hypertensive effects of tea in human interventions and animal studies, and to summarize the underlying mechanisms, based on ex-vivo tissue and cell culture data. During recent years, an increasing number of human population studies have confirmed the beneficial effects of tea on hypertension. However, the optimal dose has not yet been established owing to differences in the extent of hypertension, and complicated social and genetic backgrounds of populations. Therefore, further large-scale investigations with longer terms of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of hypertensive risk factors, and to determine differences in beneficial effects amongst diverse populations. Moreover, data from laboratory studies have shown that tea and its secondary metabolites have important roles in relaxing smooth muscle contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting rennin activity, and anti-vascular oxidative stress. However, the exact molecular mechanisms of these activities remain to be elucidated.

scholarly journals Understanding the Journey of Human Hematopoietic Stem Cell Development

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Akhilesh Kumar ◽  
Saritha S. D’Souza ◽  
Abir S. Thakur
Keyword(s):  
Stem Cells ◽  
Blood Cell ◽  
Hematopoietic Stem Cells ◽  
Human Blood ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Hematopoietic Stem ◽  
Hematopoietic Development

Hematopoietic stem cells (HSCs) surface during embryogenesis leading to the genesis of the hematopoietic system, which is vital for immune function, homeostasis balance, and inflammatory responses in the human body. Hematopoiesis is the process of blood cell formation, which initiates from hematopoietic stem/progenitor cells (HSPCs) and is responsible for the generation of all adult blood cells. With their self-renewing and pluripotent properties, human pluripotent stem cells (hPSCs) provide an unprecedented opportunity to createin vitromodels of differentiation that will revolutionize our understanding of human development, especially of the human blood system. The utilization of hPSCs provides newfound approaches for studying the origins of human blood cell diseases and generating progenitor populations for cell-based treatments. Current shortages in our knowledge of adult HSCs and the molecular mechanisms that control hematopoietic development in physiological and pathological conditions can be resolved with better understanding of the regulatory networks involved in hematopoiesis, their impact on gene expression, and further enhance our ability to develop novel strategies of clinical importance. In this review, we delve into the recent advances in the understanding of the various cellular and molecular pathways that lead to blood development from hPSCs and examine the current knowledge of human hematopoietic development. We also review howin vitrodifferentiation of hPSCs can undergo hematopoietic transition and specification, including major subtypes, and consider techniques and protocols that facilitate the generation of hematopoietic stem cells.

scholarly journals The role of cigarette smoke-induced epigenetic alterations in inflammation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Dandan Zong ◽  
Xiangming Liu ◽  
Jinhua Li ◽  
Ruoyun Ouyang ◽  
Ping Chen
Keyword(s):  
Cigarette Smoke ◽  
Gene Transcription ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Epigenetic Alterations ◽  
Rna Sequences ◽  
Non Coding Rna ◽  
Near Future

Abstract Background Exposure to cigarette smoke (CS) is a major threat to human health worldwide. It is well established that smoking increases the risk of respiratory diseases, cardiovascular diseases and different forms of cancer, including lung, liver, and colon. CS-triggered inflammation is considered to play a central role in various pathologies by a mechanism that stimulates the release of pro-inflammatory cytokines. During this process, epigenetic alterations are known to play important roles in the specificity and duration of gene transcription. Main text Epigenetic alterations include three major modifications: DNA modifications via methylation; various posttranslational modifications of histones, namely, methylation, acetylation, phosphorylation, and ubiquitination; and non-coding RNA sequences. These modifications work in concert to regulate gene transcription in a heritable fashion. The enzymes that regulate these epigenetic modifications can be activated by smoking, which further mediates the expression of multiple inflammatory genes. In this review, we summarize the current knowledge on the epigenetic alterations triggered by CS and assess how such alterations may affect smoking-mediated inflammatory responses. Conclusion The recognition of the molecular mechanisms of the epigenetic changes in abnormal inflammation is expected to contribute to the understanding of the pathophysiology of CS-related diseases such that novel epigenetic therapies may be identified in the near future.

scholarly journals Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
K. Selthofer-Relatić ◽  
I. Bošnjak ◽  
A. Kibel
Keyword(s):  
Vascular Dysfunction ◽  
Real Life ◽  
Microvascular Disease ◽  
Microvascular Dysfunction ◽  
Point Of View ◽  
Coronary Microvascular Dysfunction ◽  
Diabetes Mellitus Type Ii ◽  
Practice Problem ◽  
Medical Entity ◽  
Underlying Mechanisms

Obesity related coronary microvascular disease is a medical entity which is not yet fully elucidated. The pathophysiological basis of coronary microcirculatory dysfunction consists of a heterogeneous group of disorders with individual morphologic/functional/clinical presentation and prognosis. Coronary microcirculatory changes include mechanisms connected with vascular dysfunction, as well as extravascular and vasostructural changes in responses to neural, mechanical, and metabolic factors. Cardiometabolic changes that include obesity, dyslipidemia, diabetes mellitus type II, and hypertension are associated with atherosclerosis of epicardial coronary arteries and/or microvascular coronary dysfunction, with incompletely understood underlying mechanisms. In obesity, microvascular disease is mediated via adipokines/cytokines causing chronic, subclinical inflammation with (a) reduced NO-mediated dilatation, (b) changed endothelial- and smooth muscle-dependent vasoregulating mechanisms, (c) altered vasomotor control with increased sympathetic activity, and (d) obesity related hypertension with cardiomyocytes hypertrophy and impaired cardiac vascular adaptation to metabolic needs. From a clinical point of view it can present itself in acute or chronic form with different prognosis, as a practice problem for real-life diagnosis and treatment.

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